Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to ...significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1β and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen species (ROS) levels in A549 and H1299 cells, and
-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.
•The multi-scale optimization strategy can serve as a conceptual material paradigm.•A giant Wrec of 5.02 J·cm−3 and a high η of ~ 90% can be obtained in the 0.5NBT-0.5SST ceramic.•The underlying ...mechanism of high energy storage properties has been visualized.
Dielectric ceramic materials with high power density and fast charge–discharge speed have attracted increasing attention in recent years. However, their mutually restricted energy density and efficiency as well as unsatisfactory temperature stability have been the main obstacles for their practical applications. Herein, a high recoverable energy density of 5.02 J·cm−3 and a high efficiency of ~ 90% can be obtained under 422 kV·cm−1 in the Sr0.85Sm0.1TiO3 (SST)-modified Na0.5Bi0.5TiO3 (NBT) ceramics via composition design and domain engineering strategy, and the excellent stability of energy storage properties in frequency (1–100 Hz) and temperature (20–180 °C) were also observed at 250 kV·cm−1 in the 0.50NBT-0.50SST ceramics, which are attributed to the improved breakdown strength (Eb) and the enhanced relaxation behavior. The increased band gap width and refined grain size are responsible for the significantly enhanced Eb of Na0.5Bi0.5TiO3-based solid solution, being confirmed by ultraviolet and visible (UV–vis) absorption spectra as well as scanning electron microscopy. The generation of polar nanoregions as demonstrated by piezoresponse force microscopy and transmission electron microscopy results in a negligible remanent polarization and thermally stable polarization-field response. It is worth noting that the energy density will be further greatly optimized due to the improvement of Eb if this ceramic composite is made into multilayer ceramic capacitor as a dielectric layer. Moreover, a large power density of 188.6 MW·cm−3 and a fast discharge speed of 70 ns can also be achieved in the optimized composition. The results show that the multi-scale optimization strategy is an effective way to realize excellent comprehensive energy storage performances in the Na0.5Bi0.5TiO3 based ceramics.
Abstract
Quantum key distribution (QKD) enables secure key exchanges between two remote users. The ultimate goal of secure communication is to establish a global quantum network. The existing field ...tests suggest that quantum networks are feasible. To achieve a practical quantum network, we need to overcome several challenges including realizing versatile topologies for large scales, simple network maintenance, extendable configuration and robustness to node failures. To this end, we present a field operation of a quantum metropolitan-area network with 46 nodes and show that all these challenges can be overcome with cutting-edge quantum technologies. In particular, we realize different topological structures and continuously run the network for 31 months, by employing standard equipment for network maintenance with an extendable configuration. We realize QKD pairing and key management with a sophisticated key control centre. In this implementation, the final keys have been used for secure communication such as real-time voice telephone, text messaging and file transmission with one-time pad encryption, which can support 11 pairs of users to make audio calls simultaneously. Combined with intercity quantum backbone and ground–satellite links, our metropolitan implementation paves the way toward a global quantum network.
Blood–brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have ...previously reported that lychee seed polyphenols (LSP) exerted anti‐neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO‐1, were examined. In addition, the inhibition of Aβ(25–35)‐induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase‐1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase‐1, IL‐1β, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aβ(25–35)‐induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase‐1, IL‐1β, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aβ(25–35)‐induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1‐mediated autophagy.
Alzheimer’s disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the ...exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aβ(1–42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aβ and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF’s benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored.
This ...study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action.
Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aβ- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed.
The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aβ- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aβ and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine).
LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE.
Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.
Fluorescent dithienylethene-based photochromic materials have been attracting considerable attention owing to their wide applications in biological and materials sciences. However, the limitations of ...detrimental UV irradiation for photocyclization, short emission lifetime, and inefficient photoresponsive speed still need to be addressed. Herein, a novel dithienylethene photochromic molecule,
BFBDTE
, has been prepared by the incorporation of a difluoroboron β-diketonate (BF
2
bdk) unit. The strong electron acceptor BF
2
bdk not only reduces the energy gap of the open isomer, ensuring visible light-controlled fluorescence switching, but also promotes intersystem crossing for the generation of thermally activated delayed fluorescence (TADF). Upon alternating irradiation with green and NIR light,
BFBDTE
presents a rare example of photochromism, fluorescence and TADF switching in various polar solvents and a poly(methyl methacrylate) (PMMA) film. Meanwhile, it shows rapid and well repeatable cyclization (12 s) and cycloreversion reactions (20 s) in PMMA, accompanied by fast TADF switching within 11 s. Furthermore, photo-electrochemical measurements reveal a remarkable on-off photoelectronic response (photocurrent density ratio:
I
light
/
I
dark
= 684) between the open- and closed-form of
BFBDTE
. These remarkable merits make
BFBDTE
promising for photoswitchable molecular devices, optical memory storage systems, NIR detectors, and photoelectric switching.
Controlled by the alternating irradiation of green and NIR light, difluoroboron modifed dithienylethene shows rapid photochromism and photoelectronic switching.
Organic–inorganic hybrid perovskite‐type multiferroics have attracted considerable research interest owing to their fundamental scientific significance and promising technological applications in ...sensors and multiple‐state memories. The recent achievements with divalent metal dicyanamide compounds revealed such malleable frameworks as a unique platform for developing novel functional materials. Herein, two 3D organic–inorganic hybrid perovskites Et3P(CH2)2FMn(dca)3 (1) and Et3P(CH2)2ClMn(dca)3 (2) (dca=dicyanamide, N(CN)2−) are presented. Accompanying the sequential phase transitions, they display a broad range of intriguing physical properties, including above room temperature ferroelastic behavior, switchable dielectricity, and low‐temperature antiferromagnetic ordering (Tc=2.4 K for both 1 and 2). It is also worth noting that the spontaneous strain value of 1 is far beyond that of 2 in the first ferroelastic phase, as a result of the precise halogen substitution. From the point view of molecular design, this work should inspire further exploration of multifunctional molecular materials with desirable properties.
Ferroelastic behavior: By using halogen substitution, two 3D organic–inorganic hybrid perovskite‐type materials Et3P(CH2)2FMn(dca)3 (1) and Et3P(CH2)2ClMn(dca)3 (2) (dca=dicyanamide, N(CN)2−, see figure) are reported. These materials display a broad range of intriguing physical properties, including above room temperature ferroelastic behavior, switchable dielectricity, and low‐temperature antiferromagnetic ordering.
Plant polysaccharides (PPS) composed of more than 10 monosaccharides show high safety and various pharmacological activities, including immunoregulatory, antitumor, antioxidative, antiaging, and ...other effects. In recent years, emerging evidence has indicated that many PPS are beneficial for metabolic diseases, such as cardiovascular disease (CVD), diabetes, obesity, and neurological diseases, which are usually caused by the metabolic disorder of fat, sugar, and protein. In this review, we introduce the common characteristics and functional activity of many representative PPS, emphasize the common risks and molecular mechanism of metabolic diseases, and discuss the pharmacological activity and mechanism of action of representative PPS obtained from plants including Aloe vera, Angelica sinensis, pumpkin, Lycium barbarum, Ginseng, Schisandra chinensis, Dioscorea pposite, Poria cocos, and tea in metabolic diseases. Finally, this review will provide directions and a reference for future research and for the development of PPS into potential drugs for the treatment of metabolic diseases.
Lymph node metastasis is a frequent occurrence in a variety of tumour forms and poses an enormous challenge to cancer treatment. This process is critical to the development of the disease and is ...frequently linked to a poor prognosis. Over 90% of cancerous cells move through lymph nodes, making them important entry routes for the spread of cancer cells. The prognosis of cancer patients is significantly impacted by lymph node metastases, which also affects treatment choices. Targeting lymph node metastases presents numerous difficulties for conventional medication delivery techniques. It is still very difficult to selectively target cancer cells in lymph nodes without risking injury to healthy organs and unforeseen consequences. Additionally, systemic delivery of drugs is hampered by the slow flow rate of lymphatic vessels. Chemotherapeutic medicines' poor solubility and stability further reduce their effectiveness when taken orally. Additionally, the extracellular matrix that surrounds lymph node tumours is extensive, which makes it difficult for conventional pharmaceutical delivery systems to reach cancer cells. The development of nanocarriers for precise drug delivery to LNs has attracted a lot of interest to overcome these obstacles. Most solid tumours first spread through the lymphatic system, hence effective drug administration to these tissues is essential for better therapeutic results. Nanocarriers have several benefits, including the capacity to pass through barriers like blood-brain barriers and membranes to reach the lymphatic system. High medication dosages can be enclosed thanks to the physicochemical characteristics of nanocarriers, such as their higher surface-to-volume ratio. Additionally, ligands, antibodies, polymers, or biological molecules can be attached to nanocarrier surfaces to change their properties, allowing for the targeted delivery of lymph node epithelial cells. This use of nanocarriers for drug delivery maximizes on-target effects and related adverse effects while improving the effectiveness of medication delivery to target locations. More research and development in this field is needed to optimize nanocarrier design, increase targeting capabilities, and expand clinical applications for better cancer care.
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